基于低毒性Mn: ZnS 量子点的活体肿瘤靶向荧光成像

For in vivo tumor fluorescence imaging,the corresponding fluorescence imaging agency must be characterized as low toxicity,tumor-targeting, good biocompatibility and photostability.To meet these requirements,integrating several functional materials to develop an integreted multifunctional fluorescence imaging agency may be a good choice, since materials with only luminescent property are inefficient. In this proposal, we intend to obtain a multifunctional fluorescent imaging agency containing Mn-doped ZnS quantum dots (Mn: ZnS QDs), phosphorylcholine (PC) and monodispersed hydroxyapatite nanoparticles (HANPs). Due to the low toxicity of Mn: ZnS QDs, tumor-targeting ability of PC and good biocompatibility of HANPs, the resulting composite material can thus meet the requirements for in vivo tumor targeted fluorescence imaging. We believe the research results will be helpful for developing multifunctional fluorescent materials as well as exploration of multifunctional fluorescent imaging agency for in vivo tumor imaging. Moreover, this proposal will also have promising prospect in clinical tumor diagnosis and treatment and nanomedicine.

良好的活体肿瘤荧光成像介质需兼顾低毒性、靶向、良好的生物相容性和优异的光稳定性等特点，但单一的发光材料难以同时满足上述要求。有效地解决这一问题的方法是将多种功能材料结合，从而发展多功能兼备的成像介质。本项目提出将不含有毒重金属的Mn掺杂ZnS量子点（Mn: ZnS QDs，作为荧光物质）、小分子磷酸胆碱（PC，作为癌细胞靶向官能团）和单分散纳米羟基磷灰石（HANPs，作为生物相容性的荧光物质载体）三种材料结合， 发展一种低毒性、靶向和生物相容性更好、成像灵敏度更高的单分散仿生纳米荧光成像介质，为建立高效灵敏的体内肿瘤荧光成像方法开展技术基础研究。本项目的实施将是对多种功能纳米材料的复合及其在活体肿瘤成像介质方面应用的一个积极和有意义的探索。此外，本项目亦对促进临床癌症诊断治疗技术和纳米医药的发展有重要的科学意义和现实意义。

基于本项目，申请者在基于掺杂量子点构建具有良好光稳定性、良好生物相容性的荧光成像介质领域开展了相关研究工作，取得了一定进展。（1）将单分散氟掺杂纳米羟基磷灰石与低毒性Mn掺杂量子点交联，构建了生物相容性良好的、低毒性荧光成像介质。该荧光成像介质不仅保留了掺杂量子点良好的发光强度和发光稳定性，还保留了纳米羟基磷灰石良好的单分散性和生物相容性。上述荧光成像介质能对两种肿瘤细胞进行很好的胞内成像和染色，显示了其在癌症诊断等生物医学领域的潜在应用前景；（2）通过双富集策略，将Cu掺杂量子点组装到SiO2表面，构建了高亮度的生物相容性良好的荧光成像介质。结果表明，上述双富集策略对掺杂量子点的荧光信号具有很好的放大及增强效果，显示出上述荧光成像介质在高灵敏肿瘤细胞成像、超灵敏生物检测等领域的应用前景。